As part of our continuing effort to understand both the evolution and the structure-function relationships of the major histocompatibility antigens of the mouse, we have been involved in a number of studies applying the methods of recombinant DNA technology to the genes that encode these cell surface proteins. In particular, we have focussed on: A. The identification of genes highly homologous to (and thus, possibly allelic to) the H-2L gene of the BALB/c mouse in other inbred mouse strains and in wild mice as well. We have demonstrated a similar gene in virtually all mouse DNA that we have examined, and have cloned one such example from the C57B1/6 mouse. B. The analysis of the recombinational events that occur between fragments of H-2 genes when they are introduced into mouse L cells by the method of calcium phosphate precipitation. Even in the absence of selective pressure, these tissue culture cells are capable of generating active and unique H-2 genes from exposure to overlapping parts of H-2Dd and H-2Ld or vice versa. This provides a novel system for generating H-2 mutant gene products for analysis of their function. C. The development of methods for introducing mouse class II (I-A) genes into either functional B cell lymphoma lines, or into mouse L cells. Surprisingly, the fibroblastoid L cells are capable of assuming the function of antigen-presenting cells when they are converted to I-A positive cells by such transfection procedures. D. Generating in vitro recombinant chimeric class II/class I genes with the intent of analyzing 1) the requirements for cell surface expression of MHC gene products, and 2) the role of particular domains of the class II or class I molecules in T cells recognition. E. Developing a molecular biological approach to the cloning of genes linked to and/or encoding the Mls locus of the mouse, located on chromosome 1, which is the only known non-major histocompatibility complex locus controlling a primary T cell proliferative response.